The present invention relates to apparatus for inhaler testing, and in particular to apparatus for dry powder inhaler (DPI) testing.
The vast majority of Dry Powder Inhalers (DPIs) are classified as “passive” breath actuated devices; that is to say, they rely solely on the patient's inspiration to operate. There is no necessity to co-ordinate breathing with the actuation—the patient simply inhales deeply to access the drug. It follows that both the delivered and fine particle dose of DPIs are dependent on the strength and duration of the patient's inspiration, a critical quality attribute (CQA) which must be simulated during the course of in vitro testing. The testing of DPIs is further complicated by the fact that different inhalers provide varying degrees of resistance to flow i.e. some require more effort to inhale than others.
In the case of the in vitro testing of DPIs, the European and US pharmacopoeias specify that the duration of a single inhalation cycle (equivalent to that of a typical user when inhaling the drug) be achieved through the use of a 2-way switching valve connected to a vacuum pump. The operation of the switching valve, and hence the duration of the breathing cycle, is controlled by means of a timer. One side of the valve is connected to either the sampling apparatus (in the case of delivered dose) or a cascade impactor (in the case of particle size determination) and the other to a vacuum pump. In pre-test mode, the switching valve is in the closed position such that no flow passes through the test apparatus. On initiation of the test, the 2-way valve switches such that flow now passes through the test apparatus and hence the inhaler under test. On expiration of the pre-set time, the solenoid closes again and the “inhalation” cycle is complete.
In the in vitro case, the in vivo strength and duration of the user's inspiration is replicated by the flow rate used and the time for which the solenoid valve concerned remains open. To establish the correct flow rate to be used, it is first necessary to establish the flow rate required to produce a pressure drop comparable with that found at the mouth of the user in vivo when using the particular inhaler being studied. Both European and US Pharmacopoeias suggest a pressure drop over the inhaler of 4 kPa as being broadly representative of the pressure drop generated during inhalation by adult patients using DPIs. The pressure drop created by the air drawn through an inhaler can be measured directly by measuring the absolute pressure downstream of the inhaler mouthpiece and comparing this directly with atmospheric pressure.
It is known to use a flow control valve to manually adjust the flow rate from the vacuum pump to produce the required pressure drop of 4 kPa and then, by replacing the inhaler with a suitable flow meter, to measure the flow rate, Q, required to produce this pressure drop. It is this flow rate, Q, that the Pharmacopoeias state should be used for the determination of both delivered dose uniformity and aerodynamic particle size distribution. The only exception to this criterion is that if the flow required to produce a 4 kPa pressure drop is >100 L/min, as for example in the case of particularly low resistance inhalers, whereupon 100 L/min should be used.
An example of existing apparatus used to perform this testing is the Copley Critical Flow Controller Series TPK available from Copley Scientific. Whilst existing products which perform the aforementioned testing more than adequately perform their function, the requirement to manually adjust a flow control valve is prone to inaccuracies caused by manual adjustment of the valve, and hence can be time consuming.